One of the most exciting developments in environmental science and technology is the emerging field of exposomics, i.e., rapid and sensitive detection of large sets of analytes (exposome) reflecting the complexity of exposure in the personal environment using human specimens including blood, urine, and saliva, which are likely to be available from both prospective and retrospective epidemiological cohorts. However, technology platforms that could perform high-sensitivity, high-specificity, and multi-analyte detection of these samples, particularly in small volumes, are currently lacking. Liquid chromatography-electrospray ionization mass spectrometry (LC-ESI/MS) is the most powerful technique for large-scale quantitative and qualitative analyses of proteins and metabolites, i.e., proteomics and metabolomics. Although a variety of mass spectrometry approaches have been used in the National Biomonitoring Program (NBP), they typically require relatively large sample volumes for blood and serum analyses because of the extremely low concentrations of target analytes. This renders them impractical for population studies of multiple analytes where very small volumes of blood are collected. In response to RFA-ES-12-004, Newomics Inc. proposes to develop fully- integrated microfluidic chips, as a new platform for rapid and sensitive biomonitoring in humans. The chip is built on micro fabricated monolithic multinozzle emitters and multinozzle emitter array chips for nano-ESI-MS, which collectively offer a straightforward yet novel solution to the longstanding problem of the efficient coupling between the silicon microfluidic chip and ESI-MS, and pave the way for the large-scale integration proposed in this SBIR project. The proposed microchips will monolithically interface on-chip solid-phase microextraction (SPME)/solid-phase extraction (SPE) with on-chip/on-line liquid chromatography (LC)-nanoelectrospray mass spectrometry (nano-ESI-MS). The SPME/SPE-LC-MS chips will serve as a low-cost universal platform for enabling high-sensitivity, high-specificity, high-throughput, multiplexed, and multi-analyte biomonitoring using small volumes of human blood. This in turn will offer new opportunities for epidemiologic studies which seek to characterize individual exposomes through MS-based metabolomics, proteomics and/or adductomics analyses of human biospecimens. PUBLIC HEALTH RELEVANCE: Cutting-edge technologies enable breakthroughs in biomedical research. Developments of mass spectrometry-based microchip platforms for rapid and sensitive biomonitoring in humans will improve risk assessment of personal exposure to environmental toxins, and thereby providing new strategies for public health.